Proton Stimulation Targeting Plaque Magnetite Reduces Amyloid-β Plaque and Iron Redox Toxicity and Improves Memory in an Alzheimer’s Disease Mouse Model

• Published in: Journal of Alzheimer's disease 2021-01, Vol.84 (1), p.377-392
• Main Authors: Seo, Seung-Jun, Chang, Won-Seok, Jeon, Jae-Geun, Choi, Younshick, Kim, EunHo, Kim, Jong-Ki
• Format: Article
• Language: English
• Subjects: Age; Alzheimer Disease - pathology; Alzheimer Disease - radiotherapy; Alzheimer's disease; Animals; Brain; Brain - pathology; Coexistence; Cognitive ability; Disease Models, Animal; Electron emission; Emission analysis; Emissions control; Female; Ferrosoferric Oxide - metabolism; Fibrils; Hippocampus; Histochemical analysis; Humans; Iron - toxicity; Magnetite; Memory; Memory - physiology; Mice; Mice, Transgenic; Neurodegenerative diseases; Oxidation-Reduction; Plaque, Amyloid - pathology; Proteins; Proton beams; Proton Therapy; Recovery (Medical); Senile plaques; Stimulation; Toxicity; β-Amyloid
• ISSN: 1387-2877; 1875-8908
• DOI: 10.3233/JAD-210739

Background: The coexistence of magnetite within protein aggregates in the brain is a typical pathologic feature of Alzheimer’s disease (AD), and the formation of amyloid-β (Aβ) plaques induces critical impairment of cognitive function. Objective: This study aimed to investigate the therapeutic effect of proton stimulation (PS) targeting plaque magnetite in the transgenic AD mouse brain. Methods: A proton transmission beam was applied to the whole mouse brain at a single entrance dose of 2 or 4 Gy to test the effect of disruption of magnetite-containing Aβ plaques by electron emission from magnetite. The reduction in Aβ plaque burden and the cognitive function of the PS-treated mouse group were assayed by histochemical analysis and memory tests, respectively. Aβ-magnetite and Aβ fibrils were treated with PS to investigate the breakdown of the amyloid protein matrix. Results: Single PS induced a 48–87%reduction in both the amyloid plaque burden and ferrous-containing magnetite level in the early-onset AD mouse brain while saving normal tissue. The overall Aβ plaque burden (68–82%) and (94–97%) hippocampal magnetite levels were reduced in late onset AD mice that showed improvements in cognitive function after PS compared with untreated AD mice (p